Abstract: Alzheimer ’s disease (AD) is the most common form of dementia, affecting over 50 million people worldwide. This figure is projected to nearly double every 20 years, reaching 82 million by 2030 and 152 million by 2050 (Alzheimer’s Disease International). The apolipoprotein ε4 (APOE4) allele is the strongest genetic risk factor for late-onset AD (after age 65 years). Apolipoprotein E, a lipid transporter, exists in three variants: ε2, ε3, and ε4. APOE ε2 (APOE2) is protective against AD, APOE ε3 (APOE3) is neutral, while APOE4 significantly increases the risk. Individuals with one copy of APOE4 have a 4-fold greater risk of developing AD, and those with two copies face an 8-fold risk compared to non-carriers. Even in cognitively normal individuals, APOE4 carriers exhibit brain metabolic and vascular deficits decades before amyloid-beta (Aβ) plaques and neurofibrillary tau tangles emerge—the hallmark pathologies of AD (Reiman et al., 2001, 2005; Thambisetty et al., 2010). Notably, studies have demonstrated reduced glucose uptake, or hypometabolism, in brain regions vulnerable to AD in asymptomatic middle-aged APOE4 carriers, long before clinical symptoms arise (Reiman et al., 2001, 2005).